B cell zone reticular cell microenvironments shape CXCL13 gradient formation

Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13 + follicular reticular cells...

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Veröffentlicht in:	Nature communications Jg. 11; H. 1; S. 3677 - 15
Hauptverfasser:	Cosgrove, Jason, Novkovic, Mario, Albrecht, Stefan, Pikor, Natalia B., Zhou, Zhaoukun, Onder, Lucas, Mörbe, Urs, Cupovic, Jovana, Miller, Helen, Alden, Kieran, Thuery, Anne, O’Toole, Peter, Pinter, Rita, Jarrett, Simon, Taylor, Emily, Venetz, Daniel, Heller, Manfred, Uguccioni, Mariagrazia, Legler, Daniel F., Lacey, Charles J., Coatesworth, Andrew, Polak, Wojciech G., Cupedo, Tom, Manoury, Bénedicte, Thelen, Marcus, Stein, Jens V., Wolf, Marlene, Leake, Mark C., Timmis, Jon, Ludewig, Burkhard, Coles, Mark C.
Format:	Journal Article
Sprache:	Englisch
Veröffentlicht:	London Nature Publishing Group UK 22.07.2020 Nature Publishing Group Nature Portfolio
Schlagworte:	13 13/31 13/51 14 14/19 631/250/1619/40 631/250/1620/1616 631/250/2503 631/250/98 64 64/60 Adaptive Immunity Animals B-Lymphocytes - cytology B-Lymphocytes - immunology B-Lymphocytes - metabolism Cancer Cathepsin B Cathepsin B - genetics Cathepsin B - metabolism Cell Behavior Cell Line Cellular Biology Cellular Microenvironment - immunology Chemokine CXCL13 - immunology Chemokine CXCL13 - metabolism Chemokines Computer Simulation Concentration gradient CXCL13 protein Dendritic Cells, Follicular - cytology Dendritic Cells, Follicular - immunology Dendritic Cells, Follicular - metabolism Extracellular matrix Extracellular Matrix - metabolism Homing behavior Humanities and Social Sciences Humans Immunology Innate immunity Life Sciences Lymph nodes Lymphatic system Mathematical models Mice Mice, Knockout Microenvironments Microscopy, Fluorescence Models, Biological multidisciplinary Nodes Optimization Palatine Tonsil - cytology Phenotypes Recombinant Proteins - genetics Recombinant Proteins - immunology Recombinant Proteins - metabolism Science Science (multidisciplinary) Solubilization Stromal Cells - immunology Stromal Cells - metabolism
ISSN:	2041-1723, 2041-1723
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Zusammenfassung:	Through the formation of concentration gradients, morphogens drive graded responses to extracellular signals, thereby fine-tuning cell behaviors in complex tissues. Here we show that the chemokine CXCL13 forms both soluble and immobilized gradients. Specifically, CXCL13 + follicular reticular cells form a small-world network of guidance structures, with computer simulations and optimization analysis predicting that immobilized gradients created by this network promote B cell trafficking. Consistent with this prediction, imaging analysis show that CXCL13 binds to extracellular matrix components in situ, constraining its diffusion. CXCL13 solubilization requires the protease cathepsin B that cleaves CXCL13 into a stable product. Mice lacking cathepsin B display aberrant follicular architecture, a phenotype associated with effective B cell homing to but not within lymph nodes. Our data thus suggest that reticular cells of the B cell zone generate microenvironments that shape both immobilized and soluble CXCL13 gradients. Morphogens such as chemokines form gradients to direct graded responses and modulate cell behaviors. Here the authors show, using imaging and computer simulation, that the chemokine CXCL13 originated from follicular reticular cells in the lymph nodes forms both soluble and immobilized gradients to regulate B cell recruitment and migration.
Bibliographie:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 14 content type line 23
ISSN:	2041-1723 2041-1723
DOI:	10.1038/s41467-020-17135-2